A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosome abnormality. Although polygenic disorders are the most common, the term is mostly used when discussing disorders with a single genetic cause, either in a gene or chromosome. The mutation responsible can occur spontaneously before embryonic development, or it can be inherited from two parents who are carriers of a faulty gene or from a parent with the disorder. When the genetic disorder is inherited from one or both parents, it is also classified as a hereditary disease. Some disorders are caused by a mutation on the X chromosome and have X-linked inheritance. Very few disorders are inherited on the Y chromosome or mitochondrial DNA.
Noonan syndrome (NS) is a genetic disorder that may present with mildly unusual facial features, short height, congenital heart disease, bleeding problems, and skeletal malformations. Facial features include widely spaced eyes, light-colored eyes, low-set ears, a short neck, and a small lower jaw. Heart problems may include pulmonary valve stenosis. The breast bone may either protrude or be sunken, while the spine may be abnormally curved. Intelligence is often normal. Complications of NS can include leukemia.
Spinal tumors are neoplasms located in either the vertebral column or the spinal cord. There are three main types of spinal tumors classified based on their location: extradural and intradural. Extradural tumors are located outside the dura mater lining and are most commonly metastatic. Intradural tumors are located inside the dura mater lining and are further subdivided into intramedullary and extramedullary tumors. Intradural-intramedullary tumors are located within the dura and spinal cord parenchyma, while intradural-extramedullary tumors are located within the dura but outside the spinal cord parenchyma. The most common presenting symptom of spinal tumors is nocturnal back pain. Other common symptoms include muscle weakness, sensory loss, and difficulty walking. Loss of bowel and bladder control may occur during the later stages of the disease.
Neurofibromatosis type I (NF-1), or von Recklinghausen syndrome, is a complex multi-system human disorder caused by the mutation of neurofibromin 1 (NF-1), a gene on chromosome 17 that is responsible for production of a protein (neurofibromin) which is needed for normal function in many human cell types. NF-1 causes tumors along the nervous system which can grow anywhere on the body. NF-1 is one of the most common genetic disorders and is not limited to any person's race or sex. NF-1 is an autosomal dominant disorder, which means that mutation or deletion of one copy of the NF-1 gene is sufficient for the development of NF-1, although presentation varies widely and is often different even between relatives affected by NF-1.
In genetics, expressivity is the degree to which a phenotype is expressed by individuals having a particular genotype. Alternatively, it may refer to the expression of a particular gene by individuals having a certain phenotype. Expressivity is related to the intensity of a given phenotype; it differs from penetrance, which refers to the proportion of individuals with a particular genotype that share the same phenotype.
A malignant peripheral nerve sheath tumor (MPNST) is a form of cancer of the connective tissue surrounding peripheral nerves. Given its origin and behavior it is classified as a sarcoma. About half the cases are diagnosed in people with neurofibromatosis; the lifetime risk for an MPNST in patients with neurofibromatosis type 1 is 8–13%. MPNST with rhabdomyoblastomatous component are called malignant triton tumors.
Neurofibromatosis type II is a genetic condition that may be inherited or may arise spontaneously, and causes benign tumors of the brain, spinal cord, and peripheral nerves. The types of tumors frequently associated with NF2 include vestibular schwannomas, meningiomas, and ependymomas. The main manifestation of the condition is the development of bilateral benign brain tumors in the nerve sheath of the cranial nerve VIII, which is the "auditory-vestibular nerve" that transmits sensory information from the inner ear to the brain. Besides, other benign brain and spinal tumors occur. Symptoms depend on the presence, localisation and growth of the tumor(s). Many people with this condition also experience vision problems. Neurofibromatosis type II is caused by mutations of the "Merlin" gene, which seems to influence the form and movement of cells. The principal treatments consist of neurosurgical removal of the tumors and surgical treatment of the eye lesions. Historically the underlying disorder has not had any therapy due to the cell function caused by the genetic mutation.
A neurofibroma is a benign nerve-sheath tumor in the peripheral nervous system. In 90% of cases, they are found as stand-alone tumors, while the remainder are found in persons with neurofibromatosis type I (NF1), an autosomal-dominant genetically inherited disease. They can result in a range of symptoms from physical disfiguration and pain to cognitive disability.
Phakomatoses, also known as neurocutaneous syndromes, are a group of multisystemic diseases that most prominently affect structures primarily derived from the ectoderm such as the central nervous system, skin and eyes. The majority of phakomatoses are single-gene disorders that may be inherited in an autosomal dominant, autosomal recessive or X-linked pattern. Presentations may vary dramatically between patients with the same particular syndrome due to mosaicism, variable expressivity, and penetrance.
The Crowe sign or Crowe's sign is the presence of axillary (armpit) freckling in people with neurofibromatosis type I. These freckles occur in up to 30% of people with the disease and their presence is one of six diagnostic criteria for neurofibromatosis. Freckles can also be present in the intertriginous area in neurofibromatosis, such as the inguinal fold, submammary areas, and nape of the neck.
The Children's Tumor Foundation (CTF) is a 501(c)(3) foundation dedicated to improving the health and well-being of individuals and families affected by NF, a group of genetic conditions known as neurofibromatosis or schwannomatosis. Their four-part mission includes propelling drug research and development through a series of strategic investments, strengthening patient support, increasing public awareness of NF and establishing best practices in clinical care for affected individuals. The Foundation is incorporated in all 50 states with active chapters and affiliates in 37 states. CTF is the largest private funder of all forms of NF research.
Costello syndrome, also called faciocutaneoskeletal syndrome or FCS syndrome, is a rare genetic disorder that affects many parts of the body. It is characterized by delayed development and intellectual disabilities, distinctive facial features, unusually flexible joints, and loose folds of extra skin, especially on the hands and feet. Heart abnormalities are common, including a very fast heartbeat (tachycardia), structural heart defects, and overgrowth of the heart muscle. Infants with Costello syndrome may be large at birth, but grow more slowly than other children and have difficulty feeding. Later in life, people with this condition have relatively short stature and many have reduced levels of growth hormones. It is a RASopathy.
Schwannomatosis is an extremely rare genetic disorder closely related to the more-common disorder neurofibromatosis (NF). Originally described in Japanese patients, it consists of multiple cutaneous schwannomas, central nervous system tumors, and other neurological complications, excluding hallmark signs of NF. The exact frequency of schwannomatosis cases is unknown, although some populations have noted frequencies as few as 1 case per 1.7 million people.
Noonan syndrome with multiple lentigines (NSML) which is part of a group called Ras/MAPK pathway syndromes, is a rare autosomal dominant, multisystem disease caused by a mutation in the protein tyrosine phosphatase, non-receptor type 11 gene (PTPN11). The disease is a complex of features, mostly involving the skin, skeletal and cardiovascular systems, which may or may not be present in all patients. The nature of how the mutation causes each of the condition's symptoms is not well known; however, research is ongoing. It is a RASopathy.
Neurofibromin (NF-1) is a protein that is encoded in the human by the NF1 gene. NF1 is located on chromosome 17. Neurofibromin, a GTPase-activating protein that negatively regulates RAS/MAPK pathway activity by accelerating the hydrolysis of Ras-bound GTP. NF1 has a high mutation rate and mutations can alter cellular growth control, and neural development, resulting in neurofibromatosis type 1. Symptoms of NF1 include disfiguring cutaneous neurofibromas (CNF), café au lait pigment spots, plexiform neurofibromas (PN), skeletal defects, optic nerve gliomas, life-threatening malignant peripheral nerve sheath tumors (MPNST), pheochromocytoma, attention deficits, learning deficits and other cognitive disabilities.
Legius syndrome (LS) is an autosomal dominant condition characterized by cafe au lait spots. It was first described in 2007 and is often mistaken for neurofibromatosis type I. It is caused by mutations in the SPRED1 gene. It is also known as neurofibromatosis type 1-like syndrome.
Sprouty-related, EVH1 domain-containing protein 1 (Spread-1) is a protein that in humans is encoded by the SPRED1 gene located on chromosome 15q13.2 and has seven coding exons.
The RASopathies are a group of developmental syndromes caused by germline mutations in genes belonging to the Ras/MAPK pathway. Common features include intellectual disability, congenital heart defects, skin abnormalities, and craniofacial abnormalities.
A microdeletion syndrome is a syndrome caused by a chromosomal deletion smaller than 5 million base pairs spanning several genes that is too small to be detected by conventional cytogenetic methods or high resolution karyotyping. Detection is done by fluorescence in situ hybridization (FISH). Larger chromosomal deletion syndromes are detectable using karyotyping techniques.
Ring chromosome 22, also known as ring 22, is a rare chromosomal disorder. Ring chromosomes occur when the ends of a chromosome lose material and fuse into a ring shape; in the case of ring 22, this occurs for chromosome 22, the last numbered human autosome. Ring chromosome 22 is marked by a number of consistent traits, such as intellectual disability, speech delay, hypotonia, and hyperactivity. The condition has a similar phenotype to Phelan-McDermid syndrome, as the loss of the SHANK3 gene is implicated in both.
